Steroid and Cytokine Regulation of Matrix Metalloproteinase Expression in Endometriosis and the Establishment of Experimental Endometriosis in Nude Mice

Kaylon L Bruner-Tran, Kaylon L. Bruner‐Tran, Esther Eisenberg, Grant R Yeaman, Ted A Anderson, Judith McBean, Judith H. McBean, Kevin G Osteen
The Journal of clinical endocrinology and metabolism · 2002 · vol. 87(10) , pp. 4782–4791 · doi:10.1210/jc.2002-020418 · PMID:12364474 · W1986891553
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Endometriotic tissues show altered MMP regulation and progesterone insensitivity, but retinoic acid and TGF-beta restore suppressed MMPs and prevent disease establishment in mice.

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Abstract

The cyclic expression of matrix metalloproteinases (MMPs) by human endometrium has been suggested to play a role in the invasive process necessary to establish endometriosis. The ability of progesterone exposure to inhibit endometrial MMP-3 and MMP-7 expression requires the local action of TGF beta and may also be linked to the local production of retinoic acid by stromal cells. A continuous expression of several MMPs in endometriotic lesions has been reported, indicating a failure of progesterone or locally produced factors to suppress these enzymes. To address cell-specific MMP regulation associated with endometriosis, we examined expression of MMP-3 and MMP-7 mRNA in eutopic endometrium and endometriotic lesions acquired during the secretory phase of the menstrual cycle. We examined the in vitro regulation of MMP-3 and MMP-7 protein in similar tissues. We also examined the in vitro regulation of MMP secretion by progesterone, retinoic acid, and TGF beta in endometriosis tissues relative to the establishment of experimental disease. Our studies indicate that either eutopic or ectopic tissue from women with endometriosis exhibit patterns of altered MMP regulation in vivo. A lack of responsiveness to progesterone was demonstrated in vitro, associated with a failure to suppress MMP expression and an enhanced ability of the tissue to establish experimental endometriosis. However, in vitro treatments with retinoic acid and TGF beta restored the ability of progesterone to suppress MMPs in vitro and prevented the establishment of experimental disease.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Gene Expression Regulation Metalloendopeptidases Progesterone Transforming Growth Factor beta Adolescent Adult Animals Endometriosis Endometrium Endometrium Estradiol Estradiol Female Gene Expression Regulation Humans In Situ Hybridization Matrix Metalloproteinase 3 Matrix Metalloproteinase 3 Matrix Metalloproteinase 7

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